Methods have been developed for the assay of the catecholamine metabolites, 3-methoxy-4-hydroxy phenylglycol, dihydroxyphenylglycol and dihydroxymandelic acid in plasma by gas chromatography-mass spectrometry. In the monkey, intravenously administered deuterated 3-methoxy-4-hydroxy phenylglycol is cleared rapidly from the circulation and secreted as sulfate and glucuronide conjugates with 30-40% conversion to vanillylmandelic acid. In normal human subjects, plasma free dihydroxyphenylglocol is 200 pg/ml and dihydroxymandelic acid 700 pg/ml. The metabolites provide an index of the activity of noradrenergic neurones in both the peripheral and central nervous systems under a variety of pathophysiological situations. Deuterated methinoine administered to controls and patients with altered norepinephrine metabolism will be analyzed for normetanephrine and metanephrine by gas liquid chromatography-mass spectrometry. Changes due to a phenylethanolamine-N-methyl transferase (PNMT) inhibitor will be studied.